Compounds and formulations for the treatment of wounds

Abstract

The present invention relates to the treatment of wounds. More particularly, it relates to compounds according to Formula (1) for use in methods of promoting wound healing, to formulations which incorporate these compounds and to a method of treating wounds using such compounds and formulations: wherein R 1 and R 2 may be the same or different and are selected from the group consisting of hydrogen (H) and a physiologically hydrolysable chemical group consisting of alkyl, alkyl carbonyl, alkenylcarbonyl arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, alkylether, alkenylether, arylether, and heteroarylether groups wherein the alkyl group or moiety consists of unsubstituted or substituted, straight-chain or branched-chain and cyclic alkyl groups having 2-22 carbon atoms, wherein the alkenyl moiety consists of unsubstituted and substituted, straight-chain or branched-chain and cyclic alkenyl groups having 2-22 carbon atoms, wherein the aryl moiety consists of unsubstituted and substituted phenyl, and phenalkyl groups wherein the alkyl moiety contains 1-3 carbon atoms and the phenyl moiety is unsubstituted or substituted, and the heteroaryl moiety is an aromatic 5- or 6-membered heterocyclic ring containing one or two heteroatoms selected from the group consisting of nitrogen, oxygen, and sulphur.

1 . A method of treating a wound in a patient, wherein the method comprises a step of topically administering or injecting a compound according to Formula (1), or a pharmaceutically acceptable salt or solvate thereof, to the wound of the patient: 
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  may be the same or different and are selected from the group consisting of hydrogen (H) and a physiologically hydrolysable chemical group selected from the group consisting of alkyl, alkylcarbonyl, alkenylcarbonyl arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, alkylether, alkenylether, arylether, and heteroarylether groups wherein the alkyl group or moiety consists of unsubstituted or substituted, straight-chain or branched-chain or cyclic alkyl groups having 2-22 carbon atoms, wherein the alkenyl moiety consists of unsubstituted or substituted, straight-chain or branched-chain or cyclic alkenyl groups having 2-22 carbon atoms, wherein the aryl moiety consists of unsubstituted or substituted phenyl, or phenalkyl groups wherein the alkyl moiety contains 1-3 carbon atoms and the phenyl moiety is unsubstituted or substituted, and the heteroaryl moiety is an aromatic 5- or 6-membered heterocyclic ring containing one or two heteroatoms selected from the group consisting of nitrogen, oxygen, and sulphur. 
       
     
     
         2 . A topical formulation comprising one or more compounds according to Formula (1), or pharmaceutically acceptable salts or solvates thereof: 
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  may be the same or different and are selected from the group consisting of hydrogen (H) and a physiologically hydrolysable chemical group selected from the group consisting of alkyl, alkylcarbonyl, alkenylcarbonyl arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, alkylether, alkenylether, arylether, and heteroarylether groups wherein the alkyl group or moiety consists of unsubstituted or substituted, straight-chain or branched-chain or cyclic alkyl groups having 2-22 carbon atoms, wherein the alkenyl moiety consists of unsubstituted or substituted, straight-chain or branched-chain or cyclic alkenyl groups having 2-22 carbon atoms, wherein the aryl moiety consists of unsubstituted or substituted phenyl, or phenalkyl groups wherein the alkyl moiety contains 1-3 carbon atoms and the phenyl moiety is unsubstituted or substituted, and the heteroaryl moiety is an aromatic 5- or 6-membered heterocyclic ring containing one or two heteroatoms selected from the group consisting of nitrogen, oxygen, and sulphur. 
       
     
     
         3 . The method according to  claim 1 , wherein the compound according to Formula (1) is a compound according to Formula (1 a): 
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  may be the same or different and have the same meaning as defined for  claim 1 . 
       
     
     
         4 . The method according to  claim 1 , wherein treating a wound means reducing scar formation, regenerating normal tissue and/or promoting the generation of normal tissue/skin structures. 
     
     
         5 . The method according to  claim 1 , wherein R 1  and R 2  are selected from the group consisting of H or —COR 3 , wherein R 3  is a C2 to C22 hydrocarbon group, preferably a linear C6, C7, C8, C9 or C10 alkyl group. 
     
     
         6 . The topical formulation according to  claim 2 , comprising two or more compounds according to Formula (1) wherein for one of those compounds both R 1  and R 2  are H. 
     
     
         7 . The topical formulation according to  claim 2 , comprising two or more compounds according to Formula (1) wherein for one of those compounds both R 1  and R 2  are —COR 3  wherein R 3  is a linear C6, C7, C8, C9 or C10 alkyl group. 
     
     
         8 . The topical formulation according to  claim 2 , comprising two or more compounds according to Formula (1) wherein for one of those compounds both R 1  and R 2  are H and for a second of those compounds both R 1  and R 2  are —COR 3  wherein R 3  is a linear C6, C7, C8, C9 or C10 alkyl group. 
     
     
         9 . The topical formulation according to  claim 2 , wherein the formulation is a lotion, cream, gel, or ointment. 
     
     
         10 . The topical formulation according to  claim 2 , further comprising a skin penetration agent. 
     
     
         11 . The topical formulation according to  claim 2 , wherein the wound is an open or closed acute wound and the method comprises applying the formulation to the wound bed within 1 hour of the wound being formed. 
     
     
         12 . A composition comprising isosorbide and at least one compound according to Formula (1) or Formula (1a), or a pharmaceutically acceptable salt or solvate thereof: 
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  may be the same or different and are selected from the group consisting of hydrogen (H) and a physiologically hydrolysable chemical group selected from the group consisting of alkyl, alkylcarbonyl, alkenylcarbonyl arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, alkylether, alkenylether, arylether, and heteroarylether groups wherein the alkyl group or moiety consists of unsubstituted or substituted, straight-chain or branched-chain or cyclic alkyl groups having 2-22 carbon atoms, wherein the alkenyl moiety consists of unsubstituted or substituted, straight-chain or branched-chain or cyclic alkenyl groups having 2-22 carbon atoms, wherein the aryl moiety consists of unsubstituted or substituted phenyl, or phenalkyl groups wherein the alkyl moiety contains 1-3 carbon atoms and the phenyl moiety is unsubstituted or substituted, and the heteroaryl moiety is an aromatic 5- or 6-membered heterocyclic ring containing one or two heteroatoms selected from the group consisting of nitrogen, oxygen, and sulphur, provided that at least one of R 1  and R 2  is a physiologically hydrolysable chemical group. 
       
     
     
         13 . The composition according to  claim 12 , wherein R 1  and R 2  are the same or different and are selected from the group consisting of hydrogen (H) and —COR 3  provided that at least one of R 1  and R 2  is —COR 3 , wherein R 3  is a linear or branched C2 to C22 alkyl. 
     
     
         14 . The composition according to  claim 13 , wherein both R 1  and R 2  are —COR 3 . 
     
     
         15 . The composition according to  claim 13 , wherein R 3  is a linear C6, C7, C8, C9 or C10 alkyl group. 
     
     
         16 . An adhesive patch or suture comprising at least one compound according to Formula (1) or (1a), or a pharmaceutically acceptable salt or solvate thereof: 
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  may be the same or different and are selected from the group consisting of hydrogen (H) and a physiologically hydrolysable chemical group selected from the group consisting of alkyl, alkylcarbonyl, alkenylcarbonyl arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, alkylether, alkenylether, arylether, and heteroarylether groups wherein the alkyl group or moiety consists of unsubstituted or substituted, straight-chain or branched-chain or cyclic alkyl groups having 2-22 carbon atoms, wherein the alkenyl moiety consists of unsubstituted or substituted, straight-chain or branched-chain or cyclic alkenyl groups having 2-22 carbon atoms, wherein the aryl moiety consists of unsubstituted or substituted phenyl, or phenalkyl groups wherein the alkyl moiety contains 1-3 carbon atoms and the phenyl moiety is unsubstituted or substituted, and the heteroaryl moiety is an aromatic 5- or 6-membered heterocyclic ring containing one or two heteroatoms selected from the group consisting of nitrogen, oxygen, and sulphur. 
       
     
     
         17 . A wound dressing comprising a carrier that is coated with a matrix having incorporated therein the compound of Formula (1) or (1a) or a pharmaceutically acceptable salt or solvate thereof or comprising a carrier that is impregnated with the compound of Formula (1) or (1a) or a pharmaceutically acceptable salt or solvate thereof: 
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  may be the same or different and are selected from the group consisting of hydrogen (H) and a physiologically hydrolysable chemical group selected from the group consisting of alkyl, alkylcarbonyl, alkenylcarbonyl arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, alkylether, alkenylether, arylether, and heteroarylether groups wherein the alkyl group or moiety consists of unsubstituted or substituted, straight-chain or branched-chain or cyclic alkyl groups having 2-22 carbon atoms, wherein the alkenyl moiety consists of unsubstituted or substituted, straight-chain or branched-chain or cyclic alkenyl groups having 2-22 carbon atoms, wherein the aryl moiety consists of unsubstituted or substituted phenyl, or phenalkyl groups wherein the alkyl moiety contains 1-3 carbon atoms and the phenyl moiety is unsubstituted or substituted, and the heteroaryl moiety is an aromatic 5- or 6-membered heterocyclic ring containing one or two heteroatoms selected from the group consisting of nitrogen, oxygen, and sulphur. 
       
     
     
         18 . The method according to  claim 1 , wherein the compound is isosorbide, isoidide, isomannide, or a combination thereof. 
     
     
         19 . The topical formulation according to  claim 2 , wherein the compound is isosorbide, isoidide, isomannide, or a combination thereof. 
     
     
         20 . The composition according to  claim 12 , wherein the compound is isosorbide, isoidide, isomannide, or a combination thereof. 
     
     
         21 . The topical formulation according to  claim 2 , wherein the compound according to Formula (1) is a compound according to Formula (1a): 
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  may be the same or different and have the same meaning as defined for  claim 2 .